异基因造血干细胞移植患者NK细胞重建与aGVHD相关性研究

The Relationship between Circulating Natural Killer Cells and Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

摘要: 目的：本研究为探讨接受异基因造血干细胞移植(allo-HSCT)的患者中，自然杀伤细胞(NK细胞)重建情况与急性移植物抗宿主病(aGVHD)的关联。方法：研究纳入安徽医科大学第一附属医院2017年6月至2023年7月期间105例allo-HSCT患者，检测其移植后+30天、+60天、+90天NK细胞计数，分析NK细胞与aGVHD发生、严重程度及预后的关联。结果：在发生aGVHD的64例患者的NK细胞计数明显低于未发生者(P < 0.05)，且发生II~IV度aGVHD的患者NK细胞水平更低(P < 0.05)。ROC曲线表明，移植后+30天、+60天、+90天NK细胞计数预测aGVHD的临界值分别为120、129.5、137.5 cells/μl (AUC分别为0.712、0.730、0.732)。生存分析显示，+60天NK细胞计数 ≥ 129.5 cells/μl组1年OS率为81.4%，显著高于<129.5 cell/μl组的56.3% (P = 0.049)；+90天NK细胞计数 ≥ 137.5 cell/μl组1年OS率达90.9%，与<137.5 cell/μl组的70.0%相比差异显著(P = 0.033)。II~IV度aGVHD患者3年OS率(19.6%)显著低于0~I度组(44.1%, P = 0.008)。预处理方案中抗胸腺细胞球蛋白(ATG)的使用及是否发生aGVHD是影响NK细胞重建的关键因素。结论：本研究证实，allo-HSCT后NK细胞重建水平与aGVHD的发生及预后密切相关，可作为早期预测aGVHD的生物标志物。

Abstract: Objective: This study aimed to explore the association between natural killer (NK) cell reconstitution and acute graft-versus-host disease (aGVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: A total of 105 patients who underwent allo-HSCT at The First Affiliated Hospital of Anhui Medical University from June 2017 to July 2023 were included. NK cell counts were detected at +30, +60 and +90 days post-transplantation, and their associations with the occurrence, severity, and prognosis of aGVHD were analyzed. Results: The NK cell counts in patients with aGVHD were significantly lower than those without aGVHD (P < 0.05), and the NK cell levels in patients with grade II~IV aGVHD were even lower (P < 0.05). Receiver operating characteristic (ROC) curve analysis showed that the cut-off values of NK cell counts for predicting aGVHD at +30, +60, and +90 days were 120, 129.5, and 137.5 cells/μl, respectively (with areas under the curve [AUC] of 0.712, 0.730, and 0.732, respectively). Survival analysis revealed that the 1-year overall survival (OS) rate in the group with NK cell count ≥ 129.5 cells/μl at +60 days was 81.4%, which was significantly higher than that in the group with NK cell count < 129.5 cells/μl (56.3%, P = 0.049). Additionally, the 1-year OS rate in the group with NK cell count ≥ 137.5 cells/μl at +90 days reached 90.9%, which was significantly different from that in the group with NK cell count < 137.5 cells/μl (70.0%, P = 0.033). The 3-year OS rate in patients with grade II~IV aGVHD (19.6%) was significantly lower than that in the grade 0~I group (44.1%, P = 0.008). The use of antithymocyte globulin (ATG) in the conditioning regimen and the occurrence of aGVHD were key factors influencing NK cell reconstitution. Conclusion: This study confirms that the level of NK cell reconstitution after allo-HSCT is closely associated with the occurrence and prognosis of aGVHD, and it can serve as a biomarker for the early prediction of aGVHD.